Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N-Sulfinyl-O-(tert-butyl)hydroxylamine, t-BuONSO

Abstract

Sulfonamides have played a defining role in the history of drug development and continue to be prevalent today. In particular, primary sulfonamides are common in marketed drugs. Here we describe the direct synthesis of these valuable compounds from organometallic reagents and a novel sulfinylamine reagent, t -BuONSO. A variety of (hetero)aryl and alkyl Grignard and organolithium reagents perform well in the reaction, providing primary sulfonamides in good to excellent yields in a convenient one-step process.

Rediscovering Sulfinylamines as Reagents for Organic Synthesis

“…During our investigations into N ‐sulfinylhydroxylamine reagents, we also found that the reaction of organometallic reagents with N ‐sulfinyl‐ O ‐ tert ‐butylhydroxylamine ( t ‐BuONSO, 20 ) unexpectedly gives primary sulfonamides. [32] t ‐BuONSO, a stable colourless liquid, was prepared on over 100 mmol scale by combining commercially available tert ‐butylhydroxylamine hydrochloride with thionyl chloride and purified by distillation (Scheme 9 ). The reaction proved relatively insensitive to steric and electronic factors and was compatible with aryl and alkyl nucleophiles.…”

A magnetic porous organic polymer: catalytic application in the synthesis of hybrid pyridines with indole, triazole and sulfonamide moieties

“…[33][34][35][36] Therefore, these compounds with exceptional advantages including high stability, threedimensional shape, hydrophilic properties, favorable physicochemical properties and having incomparable potential in modern antibiotics have revolutionized the areas of medicinal chemistry. 36,37 Sulfonamide families have special antibacterial properties and were introduced as highly important antimicrobials. 38 Furthermore, the privileged properties of sulfa drug as anti-bacterial, 39 anti-fungal, 40 HIV protease inhibitory, 41 anti-inammatory, 42 anti-protozoal, 43 are well known.…”

Cycloadditions of Donor–Acceptor Cyclopropanes and ‐butanes using S=N‐Containing Reagents: Access to Cyclic Sulfinamides, Sulfonamides, and Sulfinamidines

“…[8] Sulfur has been ap opular choice of heteroatom for the reactions of D-A cyclopropanes, [9] not only because of its reactivity,but also its prevalence in important pharmaceutical compounds and natural products. [10] Sulfinylamines have recently been utilized heavily by Willis and co-workers [11] as stable starting materials for the synthesis of both sulfur(IV) and sulfur(VI) containing compounds including sulfilimines, [12] sulfonamides, [13] and sulfonimidamides. [14] Inspired by this,wedecided to explore the use of the S=Ndouble bond of sulfinylamines as a2 p component in the (n + 2)-cycloaddition reactions of D-A cyclopropanes and D-A cyclobutanes.Ease of synthesis makes sulfinylamines an attractive choice of starting material, particularly because of the possibility of having al eaving group at the nitrogen atom, thus allowing formal insertion of HNSO 2 upon cleavage and potentially of great interest as bioactive compounds,w ith isothiazolidine dioxides and isothiazolidinones already known to be useful as antirheumatic and anticancer agents.…”